The microbial metabolite desaminotyrosine protects from influenza through type I interferon

• Autores: Ashley L. Steed, George P. Christophi, Gerard E. Kaiko
• Localización: Science, ISSN 0036-8075, Vol. 357, Nº 6250, 2017, págs. 498-502
• Idioma: inglés
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• Resumen

  • The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.